Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis

Daniela Lecca, Yoo Jin Jung, Michael T Scerba, Inho Hwang, Yu Kyung Kim, Sun Kim, Sydney Modrow, David Tweedie, Shih-Chang Hsueh, Dong Liu, Weiming Luo, Elliot Glotfelty, Yazhou Li, Jia-Yi Wang, Yu Luo, Barry J Hoffer, Dong Seok Kim, Ross A McDevitt, Nigel H Greig

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

OBJECTIVE: Evaluating the efficacy of 3,6'-dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline.

BACKGROUND: Amyloid-β (Aβ) or tau-focused clinical trials have proved unsuccessful in mitigating AD-associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF-α a pivotal neuroinflammatory driver.

NEW HYPOTHESIS: AD-associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation will define the role of neuroinflammation in AD progression.

MAJOR CHALLENGES: Difficulty of TNF-α-lowering compounds reaching brain, and identification of a therapeutic-time window to preserve the beneficial role of neuroinflammatory processes.

LINKAGE TO OTHER MAJOR THEORIES: Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aβ. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.
原文英語
期刊Alzheimer's and Dementia
DOIs
出版狀態打印前電子出版 - 3月 2 2022

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